Abstract

Purpose

While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC.

Methods

Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch™ system. Different cutoffs were analyzed both for iCTC and aCTC (≥5, ≥10, ≥25 and ≥50 CTC/7.5 ml). CTCKIN were characterized by ≥25 % changes in CTC counts.

Conclusions

Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts ≥ 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTCKIN at ≥ 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.

Notes

Acknowledgments

The authors gratefully acknowledge all patients whose data were used in this study. We also thank the medical and nursing staff, especially Martina Scharpff, at the National Center for Tumor Diseases (NCT; Heidelberg) for excellent management and care of our patients; the NCT laboratory staff; and Antje Andreas; Cornelia Coith; and Oliver Mauermann (Hamburg), who provided excellent technical assistance with the CTC determinations. This study was supported by NCT in-house funds, made available to AS and AT, and by grants to AT from the BioRN Leading Edge Cluster “Molecular and Cell Based Medicine” (BRN 02GS1893), supported by the German Federal Ministry of Education and Research (BMBF), Berlin, Germany (BMBF N02/74829), and the Dietmar Hopp Foundation. Moreover, this study was supported by the ERC-2010-AdG_20100317 DISSECT to KP. We acknowledge the financial support from the German Research Foundation (DFG) and Ruprecht-Karls-Universität Heidelberg through the funding program for Open Access Publishing.